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排序方式: 共有855条查询结果,搜索用时 62 毫秒
31.
Batool Shannan Quan Chen Andrea Watters Michela Perego Clemens Krepler Rakhee Thombre Ling Li Geena Rajan Scott Peterson Phyllis A. Gimotty Melissa Wilson Katherine L. Nathanson Tara C. Gangadhar Lynn M. Schuchter Ashani T. Weeraratna Meenhard Herlyn Adina Vultur 《Pigment cell & melanoma research》2016,29(3):317-328
Targeted therapies for mutant BRAF metastatic melanoma are effective but not curative due to acquisition of resistance. PI3K signaling is a common mediator of therapy resistance in melanoma; thus, the need for effective PI3K inhibitors is critical. However, testing PI3K inhibitors in adherent cultures is not always reflective of their potential in vivo. To emphasize this, we compared PI3K inhibitors of different specificity in two‐ and three‐dimensional (2D, 3D) melanoma models and show that drug response predictions gain from evaluation using 3D models. Our results in 3D demonstrate the anti‐invasive potential of PI3K inhibitors and that drugs such as PX‐866 have beneficial activity in physiological models alone and when combined with BRAF inhibition. These assays finally help highlight pathway effectors that could be involved in drug response in different environments (e.g. p4E‐BP1). Our findings show the advantages of 3D melanoma models to enhance our understanding of PI3K inhibitors. 相似文献
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Mark P. Plummer Mark E. Finnis Liza K. Phillips Palash Kar Shailesh Bihari Vishwanath Biradar Stewart Moodie Michael Horowitz Jonathan E. Shaw Adam M. Deane 《PloS one》2016,11(11)
ObjectiveStress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness.DesignRetrospective cohort study.SettingAll adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011.PatientsStress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression.ConclusionsStress induced hyperglycemia identifies patients at subsequent risk of incident diabetes. 相似文献
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Bret Wankel Jiangyong Ouyang Xuemei Guo Krassimira Hadjiolova Jeremy Miller Yi Liao Daniel Kai Long Tham Rok Romih Leonardo R. Andrade Iwona Gumper Jean-Pierre Simon Rakhee Sachdeva Tanya Tolmachova Miguel C. Seabra Mitsunori Fukuda Nicole Schaeren-Wiemers Wan Jin Hong David D. Sabatini Xue-Ru Wu Xiangpeng Kong Gert Kreibich Michael J. Rindler Tung-Tien Sun 《Molecular biology of the cell》2016,27(10):1621-1634
Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show that the UP-delivering FVs contained Rab8/11 and Rab27b/Slac2-a, which mediate apical transport along actin filaments. Subsequently a Rab27b/Slp2-a complex mediated FV–membrane anchorage before SNARE-mediated and MAL-facilitated apical fusion. We also show that keratin 20 (K20), which forms a chicken-wire network ∼200 nm below the apical membrane and has hole sizes allowing FV passage, defines a subapical compartment containing FVs primed and strategically located for fusion. Finally, we show that Rab8/11 and Rab27b function in the same pathway, Rab27b knockout leads to uroplakin and Slp2-a destabilization, and Rab27b works upstream from MAL. These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking. 相似文献
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A combination of spectroscopic, calorimetric, and microscopic studies to understand the effect of hydroxyproline on the thermal stability, conformation, biological activity, and aggregation of proteins has been investigated. Significantly increased protein stability and suppression of aggregation is achieved in the presence of hydroxyproline. For example, exceptional increase in the thermal stability of lysozyme up to 26.4 degrees C and myoglobin up to 31.8 degrees C is obtained in the presence of hydroxyproline. The increased thermal stability of the proteins is observed to be accompanied with significant rise of the catalytic activity. Hydroxyproline is observed to prevent lysozyme fibril formation in vitro. Fluorescence and circular dichroism studies indicate induction of tertiary structures of the studied proteins in the presence of hydroxyproline. Preferential hydration of the native state is found to be crucial for the mechanism of protein stabilization by hydroxyproline. We compared the effect of hydroxyproline to that of proline and observed similar increase in the activity and suppression of protein aggregation. The results demonstrate the use of hydroxyproline as a protein stabilizer and in the prevention of protein aggregation and fibril formation. 相似文献
38.
Scaffolds of agar and gelatin were developed using a novel entrapment method where agar and gelatin molecules mutually entrapped one another forming stable cell adhesive matrices. Glutaraldehyde was used as a crosslinking agent for gelatin. Three types of hybrid matrices were prepared using agar and gelatin in different proportions in the weight ratio of 1:1, 2:1, and 3:1. Surface characterization of dry scaffolds was carried out by scanning electron microscope. Swelling studies were carried out in phosphate buffer saline (PBS) at physiological pH 7.4. The integral stability of the scaffolds was evaluated by estimating the released disintegrated gelatin from them in PBS at pH 7.4. The attachment kinetics of the cells was evaluated by culturing mouse fibroblast cell line NIH 3T3 on films. The cytocompatibility of these matrices was determined by studying growth kinetics of NIH 3T3 cells on them and morphology of cells was observed through optical photographs taken at various days of culture. It was found that the matrices containing agar and gelatin in 2:1 weight ratio exhibited best growth kinetics. The results obtained from these studies have suggested that the above-described method is a cheap and easy way to fabricate agar-gelatin hybrid scaffolds to grow cells which can be used in various in vitro tissue engineering applications like screening of drugs. 相似文献
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Adam N. Keen Luke A. Payne Vedanta Mehta Alistair Rice Lisa J. Simpson Kar Lai Pang Armando del Rio Hernandez John S. Reader Ellie Tzima 《The Journal of cell biology》2022,221(2)
The repertoire of extratranslational functions of components of the protein synthesis apparatus is expanding to include control of key cell signaling networks. However, very little is known about noncanonical functions of members of the protein synthesis machinery in regulating cellular mechanics. We demonstrate that the eukaryotic initiation factor 6 (eIF6) modulates cellular mechanobiology. eIF6-depleted endothelial cells, under basal conditions, exhibit unchanged nascent protein synthesis, polysome profiles, and cytoskeleton protein expression, with minimal effects on ribosomal biogenesis. In contrast, using traction force and atomic force microscopy, we show that loss of eIF6 leads to reduced stiffness and force generation accompanied by cytoskeletal and focal adhesion defects. Mechanistically, we show that eIF6 is required for the correct spatial mechanoactivation of ERK1/2 via stabilization of an eIF6–RACK1–ERK1/2–FAK mechanocomplex, which is necessary for force-induced remodeling. These results reveal an extratranslational function for eIF6 and a novel paradigm for how mechanotransduction, the cellular cytoskeleton, and protein translation constituents are linked. 相似文献
40.
Bimal S Bagchi AK Das V Sinha PK Lal CS Ranjan A Gupta AK Kar SK 《Indian journal of experimental biology》2001,39(9):878-882
In a bid to characterize the antigens and immunization mechanisms which may be used to produce a protective response against L. donovani, role of lipid associated polysaccharide (LPS) antigen and whole antigen was evaluated. BALB/C mice were immunized with whole or LPS antigen in combination with one of three putative adjuvents (anti CD-2 antibody/FIA/0.85% Saline). LPS antigen emulsified in anti CD-2 antibody was found to induce significant antibodies in mice on day 28 against challenge with lethal dose of L. donovani. Immunoprophylactic properties of LPS and whole antigen was investigated on day 40 through cytokine elicitation (IL-2), MIF) in culture supernatants of spleen cells, but before that MHC-II expressed on macrophage was studied. The LPS antigen in combination with anti CD-2 antibody was found to be most immuno-reactive inducing higher MHC-II expression on macrophages which was associated with substantial rise in the level of MIF and IL-2. It coincided with decline in antibody titre in 100% mice immunized with LPS antigen while Leishmania injected as whole antigen failed to induce specific macrophage and T-cell response with all the above formulations. We surmise from our data that lipid associated polysaccharide antigen linked to anti CD-2 antibody has potential for eliciting protective immunity against Leishmania. 相似文献